Theepidermis,whichprovidesaprotectivebarrierthatundergoesaconstantrenewal,isamulti-layeredtissuewiththeproliferatingcellslocatedinthebasallayer.Ascellsleavethebasallayertheunderogsignificantdifferentiation,biochemicalandmorphologicalremodeling.Thefinaldifferentiationresultsintheformationofcorneocytes.Invitrokeratinocytesmimicthisprocess.Severalgenesmarkkeratinocytespecificdifferentiation.AmongthemostfrequentlytrackedMarkersareTransglutaminase,CystatinandInvolucrin.Thekeratinocytedifferentiationstudieshaveidentifiedandprovidedsignificantdetailregardingtheinvolvementofthreeofthe4majorMAPkinasepathways(seeMAPKinaseSignalingPathway)fromseveraldiversestimulisuchasEGF,FAS,TNFandCaliciuminflux.Thep38cascadeisrepresentedtwicesincebothp38alpha(p38)andp38delta(MAPK13)areinvolved.ThekeratinocytedifferentiationcascasedalsoprovidefordetailedstudyofthefunctionsofindividualPKCisoforms.ItisinterestingtonotethecontrastingfunctionsofthePKCisoformsinthisprocess.InrecentstudiesithasbeendeterminedthatthecPKC(conventional/classicalProteinKinaseC)isoforms,whicharecalcium-,phospholipid-,anddiacylglycerol-dependentareinhibitorywhereasthenPKC(novelProteinKinaseC)isoformswhicharecalciumindependentarestimulatoryforkeratinocytedifferentiationmarkers.OntherighthandsideisanearlierstepshowingtheupregulationloopofTRAF2.ThisstepoccurspriortotheactivationosASK1andthep38cascade.

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